Protection Against West Nile Virus by RNA Interference

通过 RNA 干扰预防西尼罗河病毒

• 批准号: 6882929
• 负责人: Raymond Allen Koski
• 金额: $ 35.19万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882929
• 关键词: West Nile virus; adeno associated virus group; animal morbidity; animal mortality; biotechnology; bioterrorism /chemical warfare; disease /disorder model; disease /disorder prevention /control; emerging infectious disease; encephalitis virus; gene delivery system; gene targeting; laboratory mouse; nonhuman therapy evaluation; small interfering RNA; therapy design /development; tissue /cell culture; transfection /expression vector; vaccine development; vaccine evaluation; vector vaccine; viral vaccines; virus load; virus replication

DESCRIPTION (provided by applicant): West Nile (WN) virus is a flavivirus that can cause fatal human encephalitis. Over the past four years, this virus has established itself across the United States. There are no approved vaccines or therapies to protect against WN virus. This project is designed to develop an effective anti-WN virus RNA interference therapy. Our hypothesis is that small interfering RNAs (siRNAs) targeting WN virus RNAs for degradation will inhibit viral replication and dissemination in vivo. Several siRNAs that inhibit WN virus in cultured cells will be identified in screening assays. The siRNAs showing robust interference in cellular assays will be evaluated in vivo using an established model of WN virus infection. The siRNAs will be expressed from adenovirus-associated virus vectors, including vectors designed to selectively target WN virus-infected cells. The AAV vectors will express siRNAs in mouse spleen, liver and brain, organs susceptible to WN virus. After WN virus challenge, the mice will be assessed for viral burden in different organs, and observed for morbidity, mortality. These experiments will provide the basis for Phase II experiments optimizing delivery of interfering RNAs to infected organs in animal models of WN virus infection.

描述（由申请人提供）：西尼罗河（WN）病毒是一种可能引起致命人类脑炎的黄病毒。在过去的四年中，该病毒在美国各地建立了自己的状态。没有批准的疫苗或疗法可以预防WN病毒。该项目旨在开发有效的抗WN病毒RNA干扰疗法。我们的假设是，针对WN病毒RNA降解的小干扰RNA（siRNA）将抑制体内病毒复制和传播。在筛选测定中将鉴定出几种抑制培养细胞中WN病毒的siRNA。在体内将使用已建立的WN病毒感染模型在体内评估表现出强大干扰的siRNA。 siRNA将从腺病毒相关病毒载体中表达，包括旨在选择性靶向WN病毒感染细胞的载体。 AAV载体将在小鼠脾脏，肝脏和脑中表达siRNA，它容易受到WN病毒的影响。在WN病毒挑战之后，将评估小鼠在不同器官中的病毒负担，并观察到发病率，死亡率。这些实验将为在WN病毒感染动物模型中优化干扰RNA的II期实验提供基础。